Neurodegeneration and Astrogliosis in the Human CA1 Hippocampal Subfield Are Related to hsp90ab1 and bag3 in Alzheimer's Disease

• Published in: International journal of molecular sciences Vol. 23; no. 1; p. 165
• Main Authors: Gonzalez-Rodriguez, Melania, Villar-Conde, Sandra, Astillero-Lopez, Veronica, Villanueva-Anguita, Patricia, Ubeda-Banon, Isabel, Flores-Cuadrado, Alicia, Martinez-Marcos, Alino, Saiz-Sanchez, Daniel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23-12-2021; MDPI
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; amyloid-β; Apoptosis Regulatory Proteins - metabolism; Astrocytes; Astrocytes - metabolism; Astrocytes - pathology; Atrophy; Atrophy - metabolism; Atrophy - pathology; Autophagy; Biomarkers; Biomarkers - metabolism; Brain; CA1 Region, Hippocampal - metabolism; cavalieri; Disease Progression; Female; GFAP; Glial fibrillary acidic protein; Gliosis; Gliosis - metabolism; Gliosis - pathology; Hippocampus; HSP90 Heat-Shock Proteins - metabolism; Hsp90 protein; Humans; Hypotheses; Magnetic resonance imaging; Male; Mass spectrometry; Mass spectroscopy; Middle Aged; Neurodegeneration; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Neuronal-glial interactions; Neurons - metabolism; Neurons - pathology; Neuropathology; Ontology; optical fractionator; Protein expression; Proteins; Proteomics; Proteomics - methods; tau; Tau protein; Volume measurement; β-Amyloid; optical fractionator; autophagy; cavalieri; amyloid-β; SWATH-MS; tau; GFAP
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23010165

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder, is characterized by executive dysfunction and memory impairment mediated by the accumulation of extracellular amyloid-β peptide (Aβ) and intracellular hyperphosphorylated tau protein. The hippocampus (HIPP) is essential for memory formation and is involved in early stages of disease. In fact, hippocampal atrophy is used as an early biomarker of neuronal injury and to evaluate disease progression. It is not yet well-understood whether changes in hippocampal volume are due to neuronal or glial loss. The aim of the study was to assess hippocampal atrophy and/or gliosis using unbiased stereological quantification and to obtain hippocampal proteomic profiles related to neurodegeneration and gliosis. Hippocampal volume measurement, stereological quantification of NeuN-, Iba-1- and GFAP-positive cells, and sequential window acquisition of all theoretical mass spectrometry (SWATH-MS) analysis were performed in AD and non-AD cases. Reduced hippocampal volume was identified using the Cavalieri probe, particularly in the CA1 region, where it correlated with neuronal loss and astrogliosis. A total of 102 downregulated and 47 upregulated proteins were identified in the SWATH-MS analysis after restrictive filtering based on an FC > 1.5 and
value < 0.01. The Hsp90 family of chaperones, particularly BAG3 and HSP90AB1, are closely related to astrocytes, indicating a possible role in degrading Aβ and tau through chaperone-mediated autophagy.